This Cophar2 study is a trial which evaluates repeated early therapeutic drug monitoring, from weeks 2 to 24, after the initiation of HAART including either indinavir/r, lopinavir/r or the new 625 mg formulation of nelfinavir twice-a-day (bid). If trough concentrations were out of the range given for each protease inhibitor (PI), the PI dose was adjusted.

Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:

treatment failure defined as viral load greater than 200 copies/ml between week 16 (W16) and week 48 (W48) (confirmed by 2 samples spiked at least 15 days apart but no more than 45 days after virological failure, assayed by 50 copies/ml method)

virological failure: viral load over 200 copies/ml between W16 and W48 (confirmed by 2 samples spiked at least 15 days apart but no more than 45 days after virological failure, assayed by 50 copies/ml method)

relationship between pharmacokinetic parameters and/or plasma concentrations and the drop of viral load between day 0 (D0) and W2 and between D0 and week 4 (W4)

relationship between pharmacokinetic parameters and viral mutations occurring during the treatment of patients with virological failure (over 1000 copies/ml after week 24 [W24])

PI pharmacokinetic parameter estimation and evaluation of variability

pharmacokinetic variability of nucleoside analogues at W2

intracellular concentration of nucleoside triphosphate derivatives at W2 (trough and maximum) and relationship between virological response and adverse events

relationship between inhibitory quotient of indinavir and virological response

Estimated Enrollment:

115

Study Start Date:

July 2002

Estimated Study Completion Date:

March 2005

Detailed Description:

Because of the large pharmacokinetic inter-patient variability of protease inhibitors (PI), therapeutic drug monitoring (TDM) of protease inhibitor (PI) has been proposed to improve efficacy and tolerance of PI-containing HAART. The objective of the Cophar2 trial is to evaluate the feasibility and the impact of an early therapeutic drug monitoring in PI-naive HIV-1 infected patients in order to warrant virological success and safety of HAART.

It is a prospective, open, multicenter trial with repeated early TDM (weeks 2, 8 or 16, 24) after the initiation of HAART including either indinavir/r (IDV), lopinavir/r (LPV) or the new 625 mg formulation of nelfinavir (NFV) bid. It was planned to include 99 PI-naïve HIV-1 infected patients over 18 years old, 33 for each PI. Concentrations were measured by HPLC in each center. If trough concentrations were out of the range of 150-500, 2500-7000 or 1500-5500 ng/ml for IDV, LPV and NFV respectively, the PI doses were adjusted possibly more than once during the first 24 weeks of follow-up. Adjustments were done by steps of one pill (200, 133/33 or 250 mg for IDV, LPV/r or NFV, respectively) bid. Failure of the strategy was defined by either two consecutive viral loads over 200 copies/ml between weeks 16 and 48, or a validated PI-related adverse event grade III or IV or a grade II diarrhoea or renal lithiasis. Patients without adverse events before week 16 were defined as assessable if they had at least the virological assessment of week 16.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients infected with HIV-1

Needing an antiretroviral treatment according to standard of care

HIV viral load greater than 1000 copies/ml

Beginning a treatment containing a PI (indinavir with or without ritonavir, nelfinavir, lopinavir + ritonavir) and 2 reverse transcriptase inhibitors

PI-naive

Antiretroviral treatment-naive or already treated with reverse transcriptase inhibitors but if the viral genotypic test does not show more than 2 major mutations (including T215Y/F, Q151M, M184V/I, V75M/S, L74V) and if 3 nucleoside analogues are still active except for didanosine.

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00122590